This invention pertains to therapeutic methods of preventing and treating bronchial spasm and bronchial constriction. This invention also pertains to compounds used in the therapeutic methods.
More than 17 million people in the U.S. now have asthma, an increase of more than 75 percent since 1980. As the number of patients has risen, so have the larger consequences of the disease. Today, asthma is one of the top reasons for hospitalization of children. It causes children to miss more than 10 million school days a year and adults to miss 3 million days at work. It is responsible for more than 10 million doctor visits a year. It is estimated that asthma will be responsible for more than 5,600 deaths this year, more than twice as many as 20 years ago.
Chronic Obstructive Pulmonary Disease (COPD) is a blockage of airflow out of the lungs. COPD encompasses emphysema, alpha antritrypsin deficiency-related (AAT) emphysema, and chronic bronchitis. Nearly 16 million Americans suffer from COPD, which is the fourth leading cause of death, claiming the lives of nearly 87,000 Americans annually.
Smoking causes approximately 80 to 90 percent of COPD cases; a smoker is 10 times more likely than a nonsmoker to die of COPD. Other known causes are frequent lung infections and exposure to air pollutants. Depending on the severity of the disease, treatments may include bronchial dilators which open up air passages in the lungs; antibiotics; and exercise to strengthen muscles. People with COPD may eventually require supplemental oxygen and may have to rely on mechanical respiratory assistance.
Emphysema causes irreversible lung damage. The walls between the air sacs within the lungs lose their ability to stretch and recoil. They become weakened and break. Elasticity of the lung tissue is lost, causing air to be trapped in the air sacs and impairing the exchange of oxygen and carbon dioxide. An estimated 1.9 million Americans have emphysema.
Symptoms of emphysema include cough, shortness of breath and an increased effort to breathe. Diagnosis is by pulmonary function tests, along with the patient""s history, examination and other tests. The quality of life for a person suffering from emphysema diminishes as the disease progresses. At the onset, there is minimal shortness of breath. Eventually, there is severe shortness of breath often leading to the total dependency on the administration of oxygen around the clock.
Alpha antitrypsin deficiency-related (AAT) emphysema, also called xe2x80x9cearly onset emphysema,xe2x80x9d is caused by the inherited deficiency of a protein called alpha 1-antitrypsin (AAT) or alpha-protease inhibitor. AAT, produce by the liver, is a xe2x80x9clung protector.xe2x80x9d In the absence of AAT, emphysema is inevitable. An estimated 50,000 to 100,000 American have AAT deficiency emphysema, primarily of northern European descent.
The onset of AAT deficiency emphysema is characterized by shortness of breath, decreased exercise capacity. Blood screening is used if the trait is known to be in the family and will determine if a person is a carrier or AAT-deficient. If children are diagnoses as AAT-deficient through blood screening, they may undergo a liver transplant to prevent the onset of AAT deficiency emphysema in their adult life.
Chronic bronchitis is an inflammation of the lining of the bronchial tubes. An estimated 13.8 million people suffer from chronic bronchitis, the sixth leading chronic condition in America. Whereas emphysema is more concentrated in the elderly, chronic bronchitis affects people of all ages. Symptoms include chronic cough, increased mucus, frequent clearing of the throat and shortness of breath. It may precede or accompany pulmonary emphysema. Treatments aimed at reducing irritation in the bronchial tubes include antibiotics and bronchial dilators.
Airway diseases such as asthma, acute bronchitis, emphysema, chronic obstructive emphysema, centrilobular emphysema, panacinar emphysema, chronic obstructive bronchitis, reactive airway disease, cystic fibrosis, bronchiectasis, acquired bronchiectasis, kartaagener""s syndrome, atelectasis, acute atelectasis, chronic atelectasis, pneumonia, legionnaires disease, psittacosis, fibrogenic dust disease, diseases due to organic dust, diseases due to irritant gases and chemicals, hypersensitivity diseases of the lung, idiopathic infiltrative diseases of the lungs and the like are generally characterized by cough, shortness of breath and an increased effort to breath.
U.S. Pat. Nos. 5,798,388; 5,939,459 and 5,952,384 issued to Katz. The Katz inventions pertain to a method for treating various disease states in mammals caused by mammalian cells involved in the inflammatory response and compositions useful in the method. The method comprises: contacting the mammalian cells participating in the inflammatory response with an inflammatory mediator; wherein the inflammatory mediator is present in an amount capable of reducing the undesired inflammatory response and is an antioxidant. The preferred inflammatory mediator is a pyruvate. Katz discloses the treatment of airway diseases of the lungs such as bronchial asthma, acute bronchitis, emphysema, chronic obstructive emphysema, centrilobular emphysema, panacinar emphysema, chronic obstructive bronchitis, reactive airway disease, cystic fibrosis, bronchiectasis, acquired bronchiectasis, kartaagener""s syndrome, atelectasis, acute atelectasis, chronic atelectasis, pneumonia, essential thrombocytopenia, legionnaires disease, psittacosis, fibrogenic dust disease, diseases due to organic dust, diseases due to irritant gases and chemicals, hypersensitivity diseases of the lung, idiopathic infiltrative diseases of the lungs and the like by inhaling pyruvate containing compositions. The pyruvate acts as an inflammatory response mediator and reduces the undesired inflammatory response in mammalian cells.
U.S. Pat. No. 5,296,370 (Martin et al.) discloses therapeutic compositions for preventing and reducing injury to mammalian cells and increasing the resuscitation rate of injured mammalian cells. In one embodiment, the therapeutic composition comprises (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof, (b) an antioxidant, and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the resuscitation of injured mammalian cells.
While the above therapeutic compositions and methods are reported to treat various conditions, none of the compositions and methods disclose or teach the bronchial dilating or bronchial spasm preventing properties of low doses of pyruvate or pyruvate precursors nor do they disclose methods of treating airway diseases with a bronchial dilating effective amount or bronchial spasm preventing amount of a pyruvate or pyruvate precursor.
The present invention pertains to a method for treating an airway condition in mammals which may be characterized by one or more of the following most common symptoms: chronic cough, increased mucus, frequent clearing of the throat, wheezing, chest tightness, coughing, gasping for breath, shortness of breath and other conditions related to bronchial constriction and bronchial spasm. The method for treating such airway condition in mammals comprises contacting the lungs with a compound selected from the group consisting of pyruvate and a pyruvate precursor; wherein the compound is present in an amount capable of producing bronchial dilation. The invention further comprises a method for treating airway condition in mammals which comprises contacting the mammalian lung with a compound selected from the group consisting of pyruvate and pyruvate precursor; wherein the compound is present in a therapeutically effective amount to prevent bronchial spasm.